Index of drugs

Treatment of major depressive episodes. Prevention of recurrence of major depressive episodes. Treatment of generalized anxiety disorder. Treatment of social phobia. Treatment of panic disorder with or without accompanying agoraphobia.

1 long-life capsules contain 37.5 mg, 75 mg or 150 mg of venlafaxine as hydrochloride.

The mechanism of antidepressant action of venlafaxine probably consists in increasing the neurotransmission activity within o.u.n. In preclinical studies, it has been demonstrated that venlafaxine and its main metabolite - O-desmethylvenlafaxine (ODV) - are potent serotonin and noradrenaline reuptake inhibitors. Venlafaxine is also a weak Dopamine reuptake inhibitor. In addition, venlafaxine and ODV reduce the β-adrenergic response after both single-dose and chronic administration. Venlafaxine does not show affinity for muscarinic, cholinergic or histamine receptors (H₁) and α₁-renergic in the rat's brainin vitro, it also does not inhibit MAO activity. researchin vitro showed that there is practically no affinity for the benzodiazepine opioid receptors. After oral administration, the drug is absorbed in at least 92% of the gastrointestinal tract. When venlafaxine is given as a prolonged-release capsule, the maximum blood concentration of venlafaxine occurs after 5.5 h, whereas ODV - after 9 h. Food does not affect the bioavailability of venlafaxine and ODV.
Total bioavailability is 40-45%, which is due to the first-pass effect in the liver. Venlafaxine undergoes extensive metabolism in the liver. It is metabolized to the main active metabolite - ODV (with the participation of CYP2D6) and to the less active metabolite - N-desmethylvenlafaxine (with the participation of CYP3A4). Venlafaxine and ODV bind to plasma proteins in 27% and 30%, respectively. Venlafaxine and its metabolites are mainly excreted by the kidneys. Approximately 87% of the administered dose is excreted within 48 h. Mean T_0,5 venlafaxine and ODV are 5 ± 2 h and 11 ± 2 h, respectively. Drug concentrations and ODV reach steady state within 3 days of oral repeated administration.

Hypersensitivity to venlafaxine or other ingredients of the preparation. Do not use together with irreversible MAO inhibitors and for at least 14 days after discontinuation. Venlafaxine therapy should be discontinued at least 7 days before treatment with irreversible MAO inhibitors.

The drug should not be used in the treatment of children and adolescents <18 years - no long-term studies on the safety of use, depth. growth, maturation, cognitive and behavioral development; moreover, in children and adolescents treated with antidepressants, suicidal behaviors (suicide attempts and suicidal thoughts) and hostility (especially aggression, rebellious behavior and anger) were more frequently observed; if a decision to treat is based on the existing clinical need, the patient should be closely monitored for signs of suicide. All patients treated with venlafaxine should be monitored for signs of suicidal ideation and behavior (especially during early recovery or after a change in the dose); this applies especially to patients <25 years of age and patients with history of suicidal behavior or thoughts. When treating patients with other mental disorders, the same precautions should be taken as when treating patients with major depressive disorder. Caution should be used in patients with a history of bipolar disorder or a family history (risk of mania or hypomania); with aggressive behavior in the interview; with increased intraocular pressure or the risk of acute narrow-angle glaucoma; with hypertension and patients in whom co-morbid conditions may deteriorate as a result of increased blood pressure (eg in patients with cardiac dysfunction); in patients whose concomitant diseases may deteriorate as a result of the acceleration of cardiac function; with recent myocardial infarction or unstable coronary artery disease; with an increased risk of severe arrhythmias; with a history of seizures (discontinuation of venlafaxine if seizures occur); with the risk of hyponatraemia and / or the syndrome of abnormal secretion of the SID antidiuretic hormone (with hypovolaemia or dehydrated, taking diuretic agents, in the elderly); with an increased risk of bleeding (e.g.taking anticoagulants, medicines that affect the function of platelets); with impaired liver function (especially severe) or renal function; Elderly. In patients treated with venlafaxine, regular monitoring of blood pressure is recommended (after initiation of therapy and after increasing the dose and periodically during treatment); in patients with existing hypertension, appropriate pressure control should be obtained before starting venlafaxine treatment. During long-term treatment periodic blood cholesterol should be measured. If the use of venlafaxine and other drugs affecting the serotoninergic neurotransmitter system is necessary, careful observation of the patient due to the possibility of serotonin syndrome (potentially life-threatening). Co-administration of venlafaxine and weight loss medicines is not recommended; Venlafaxine is not indicated for the treatment of obesity, either as monotherapy or in combination therapy with other drugs. In patients with akathisia, increasing the dose of venlafaxine may be harmful. Dry mouth, occurring during treatment with venlafaxine may increase the risk of caries - patients should be advised to take care of oral hygiene. The preparation contains granules, from which the active substance is slowly released into the gastrointestinal tract. An insoluble part of these granules is excreted and can be seen in faeces.

During pregnancy, use only if the benefits to the mother outweigh the threat to the fetus. The use of venlafaxine during pregnancy or shortly before delivery may cause withdrawal symptoms in newborns as well as side effects resulting from serotoninergic effects. In some newborns exposed to venlafaxine in the late third trimester of pregnancy, complications involving gavage, breathing support or long-term hospitalization have occurred. The results of epidemiological studies indicate that the use of serotonin reuptake inhibitors in pregnant women, especially in the third trimester, may increase the risk of persistent pulmonary hypertension of the newborn. Venlafaxine and ODV are excreted in human milk - a decision should be made to continue or terminate breastfeeding or continue or discontinue treatment, taking into account the benefits of breastfeeding and the benefits of treatment for a woman.

Very common: headache, nausea, dry mouth, excessive sweating (including night sweats). Common: increase in blood cholesterol, weight loss, unusual dreams, decreased libido, dizziness, increased muscle tone (hypertonia), insomnia, nervousness, paresthesia, sedation, tremors, confusion, depersonalization, accommodation disorders, mydriasis, vision disorders, hypertension, vasodilatation (mainly blood flushes / redness), palpitations, yawning, decreased appetite (anorexia), constipation, vomiting, ejaculation / orgasm disorders (men), erectile dysfunction (impotence), bleeding disorders menstrual (increased bleeding or increased irregular bleeding, for example, menorrhagia or uterine hemorrhage), problems with passing urine (mainly difficulties with the start of micturition), pollakiuria, asthenia (weakness), chills. Uncommon: ecchymosis, gastrointestinal bleeding, weight gain, apathy, hallucinations, myoclonic muscle contractions, agitation, disturbances of coordination and balance, taste disorders, tinnitus, orthostatic hypotension, fainting, tachycardia, bruxism, diarrhea, rash, alopecia , orgasmic disorders (women), urinary retention, hypersensitivity reactions to light. Rare: akathisia / psychomotor restlessness, convulsions, manic reactions. Frequency unknown: bleeding from mucous membranes, prolonged bleeding time, thrombocytopenia, abnormal blood composition (including agranulocytosis, aplastic anemia, neutropenia and pancytopenia), abnormal liver function tests, hyponatremia, hepatitis, syndrome of abnormal secretion of antidiuretic hormone (SIADH), increased levels of prolactin in the blood, neuroleptic malignant syndrome (NMS), serotonin syndrome, extrapyramidal reactions (including dystonia, dyskinesia), tardive dyskinesia, suicidal thoughts and behaviors, closed angle glaucoma, hypotension, QT prolongation, ventricular fibrillation, tachycardia ventricular (including torsade de pointes), pulmonary eosinophilia, pancreatitis, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, pruritus, urticaria, rhabdomyolysis, anaphylaxis.Withdrawal of the drug (especially sudden) may lead to withdrawal symptoms, such as: dizziness, sensory disturbances (including paraesthesia), sleep disorders (insomnia, intense dreams), agitation or anxiety, nausea and / or vomiting, tremor, headache . Symptoms of the serotonin syndrome may include: changes in the mental state (eg agitation, hallucinations, coma), autonomic instability (eg tachycardia, labile blood pressure, hyperthermia), neuromuscular disorders (eg hyperreflexia, lack of coordination) and (or) gastrointestinal symptoms - intestinal (eg nausea, vomiting, diarrhea).

Orally. Adults.Episodes of major depression: initially 75 mg once a day. In patients not responding to the initial dose, it may be beneficial to increase the dose to a maximum of 375 mg per day. The dose should be increased gradually at intervals of about 2 weeks or longer. In cases clinically justified by the severity of symptoms, the dose may be increased in shorter intervals, but not shorter than 4 days. Dose escalation should only be carried out after clinical evaluation. The lowest effective dose should be used. Treatment should last long enough, usually a few months or longer. Evaluate the treatment regularly, approaching each patient individually. Long-term therapy may also be suitable for preventing recurrence of major depressive episodes. In most cases, the dose recommended for preventing relapse of major depressive episodes is the same as the dose used for the treatment of the last episode of depression. The use of antidepressants should be continued for at least 6 months after achieving remission.Generalized anxiety disorder: initially 75 mg once a day. In patients not responding to the initial dose, it may be beneficial to increase the dose to a maximum of 225 mg per day. The dose should be increased gradually at intervals of about 2 weeks or longer. Dose escalation should only be carried out after clinical evaluation. The lowest effective dose should be used. Treatment should last long enough, usually a few months or longer. Evaluate the treatment regularly, approaching each patient individually.Social phobia: 75 mg once a day. There is no evidence that higher doses bring additional benefits. However, for patients not responding to the initial dose, a dose increase up to a maximum of 225 mg per day should be considered. Dosage should be increased gradually at intervals of about 2 weeks or longer. Dose escalation should only be carried out after clinical evaluation. The lowest effective dose should be used. Treatment should last long enough, usually a few months or longer. Evaluate the treatment regularly, approaching each patient individually.Panic disorder: 37.5 mg daily for 7 days, then the dose should be increased to 75 mg daily. In patients not responding to 75 mg / day, it may be beneficial to increase the dose to a maximum of 225 mg / day. The dose should be increased gradually at intervals of about 2 weeks or longer. Dose escalation should only be carried out after clinical evaluation. The lowest effective dose should be used. Treatment should last long enough, usually a few months or longer. Evaluate the treatment regularly, approaching each patient individually.Special groups of patients. Elderly patients do not need to modify the dose of the drug; the lowest effective dose should always be used and patients should be closely monitored when an increase in dose is required. In patients with mild and moderate hepatic impairment, a dose reduction of 50% should be considered, and individual dosage adjustments may be necessary. In patients with severe hepatic impairment, a dose reduction of> 50% should be considered. In patients with impaired renal function with GFR from 30 to 70 ml / min, no dose adjustment is necessary. For patients requiring hemodialysis and in patients with severe renal impairment (GFR <30 ml / min), the dose should be reduced by 50%, individual dosage adjustments may be necessary.
Kaps. for extension. release should be taken with a meal, every day at about the same time each day. They should be swallowed whole with liquid; they can not be divided, crushed, chewed or dissolved. Patients treated with venlafaxine in the form ofof immediate release may go to the treatment of capsules by the release in the nearest equivalent daily dose, eg venlafaxine in the form of with immediate release 37.5 mg administered twice a day can be replaced with a capsule. 75 mg once daily. Individual dose adjustments may be necessary.